Tumor necrosis factor stimulates fibroblast growth factor 23 levels in chronic kidney disease and non-renal inflammation.

TitreTumor necrosis factor stimulates fibroblast growth factor 23 levels in chronic kidney disease and non-renal inflammation.
Publication TypeJournal Article
Year of Publication2019
AuthorsEgli-Spichtig, D, Silva, PHenrique I, Glaudemans, B, Gehring, N, Bettoni, C, Zhang, MYH, Pastor-Arroyo, EM, Schönenberger, D, Rajski, M, Hoogewijs, D, Knauf, F, Misselwitz, B, Frey-Wagner, I, Rogler, G, Ackermann, D, Ponte, B, Pruijm, M, Leichtle, A, Fiedler, G-M, Bochud, M, Ballotta, V, Hofmann, S, Perwad, F, Föller, M, Lang, F, Wenger, RH, Frew, I, Wagner, CA
JournalKidney international
Date Published05/2019
Mots-clésbone, chronic kidney disease (CKD), cytokine, fibroblast growth factor 23 (FGF23), Inflammation, Inflammatory bowel disease, tumor necrosis factor (TNF)

Fibroblast growth factor 23 (FGF23) regulates phosphate homeostasis, and its early rise in patients with chronic kidney disease (CKD) is independently associated with all-cause mortality. Since inflammation is characteristic of CKD and associates with increased plasma FGF23 we examined whether inflammation directly stimulates FGF23. In a population-based cohort, plasma tumor necrosis factor (TNF) was the only inflammatory cytokine that independently and positively correlated with plasma FGF23. Mouse models of CKD showed signs of renal inflammation, renal FGF23 expression and elevated systemic FGF23 levels. Renal FGF23 expression coincided with expression of the orphan nuclear receptor Nurr1 regulating FGF23 in other organs. Antibody-mediated neutralization of TNF normalized plasma FGF23 and suppressed ectopic renal Fgf23 expression. Conversely, TNF administration to control mice increased plasma FGF23 without altering plasma phosphate. Moreover, in Il10-deficient mice with inflammatory bowel disease and normal kidney function, plasma FGF23 was elevated and normalized upon TNF neutralization. Thus, the inflammatory cytokine TNF contributes to elevated systemic FGF23 levels and also triggers ectopic renal Fgf23 expression in animal models of CKD.

Alternate URL


Alternate JournalKidney Int.
Citation Key / SERVAL ID9692
Peer reviewRefereed
PubMed ID31301888
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